Huyang yangkun formula protects against 4-Vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats via the Hippo–JAK2/STAT3 signaling pathway

Xie, Li; Wu, Sining; Cao, Dongdong; Li, Meifang; Liu, Jian; Nie, Guangning; Yang, Li; Yang, Hongyan

doi:10.1016/j.biopha.2019.109008

Cited by 17 publications

(19 citation statements)

References 42 publications

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“…Studies have shown that ESCs directly differentiate into female germ cells, thus reversing the depletion of ovarian follicles [ 23 – 25 ]. At the same time, the HYYKF showed its potential in promoting ovarian function [ 18 ]. In our study, both HYYKF treatment and ESCs intervention improved the ovarian function of VCD-induced POI in mice, and the combination of HYYKF and ESCs showed an advantage over single HYYKF treatment or ESC intervention in improving the ovarian function.…”

Section: Discussionmentioning

confidence: 99%

“…Final concentration of the decoction was 1.6683 kg/L. Using high-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis, it was found that the main active constituents in HYYKF include campanulin, ferulic acid, and icariin and so on [18].…”

Section: Preparation Of Hyykf Extractmentioning

confidence: 99%

“…The ratio of the seven herbs is 5:1:1:1:1:1:1. Also the formula in our previous study was shown to promote ovarian follicle developing in 4-vinylcyclonhexene diepoxide (VCD)-induced POI rats, and the gene expression of transforming growth factor beta-activated kinase 1 (TAK1) was significantly different between the the control, VCD and VCD + HYYKF groups [ 18 ]. TAK1 is an important signaling molecule in the transforming growth factor beta (TGF-β) signaling pathway, and the TGF-β signaling pathway has a wide range of regulating functions by interacting with other pathways and plays a critical role in the physiological and pathological processes of pluripotent stem cells [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Synergistic effect of Huyang Yangkun Formula and embryonic stem cells on 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in mice

Xie

et al. 2020

Chin Med

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Background: Huyang Yangkun Formula (HYYKF) was developed based on theory of traditional Chinese medicine as well as clinical experience and used to improve ovarian function of premature ovarian insufficiency (POI) patients. Transplantation of embryonic stem cells (ESCs) has great potential in improving POI, and studies have confirmed that traditional Chinese medicine promoted the treatment effect of ESCs. In the present study, we compared the effect of combining HYYKF and ESCs, single HYYKF treatment and single ESCs intervention on POI mice to explore the effect of combination of HYYKF and ESCs in improving ovarian function. Methods: C57BL/6 mice were used to create a POI model by 15-day intraperitoneal injection of 160 mg/kg of 4-vinylcyclonhexene diepoxide (VCD) and then treated with HYYKF, ESCs transplantation and combination of ESCs and HYYKF. When the treatments were finished, estrus cycle, ovarian follicle counting, serum sex hormone level, and expression of key nodes in the transforming growth factor beta/transforming growth factor beta-activated kinase 1 (TGF-β/TAK1) signaling pathway were determined. Results: Combination therapy brought down the abnormal estrus cycle rate to 5.26%, significantly lower than that of HYYKF or ESCs alone (30%, 25%, respectively). The numbers of follicles at all levels were increased significantly in the combination ESCs with HYYKF group (P < 0.05), especially that of antral follicles (P < 0.01), which was not increased significantly when HYYKF or ESCs was single used. The level of anti-Mullerian hormone (AMH) was more significantly increased in the combination ESCs with HYYKF group (P < 0.01) than that of HYYKF or ESCs alone (both P < 0.05). The expression of the key nodes TGF-β1, TAK1, JNK, Smad4 and FSHR in the TGF-β/TAK1 pathway were obviously affected in the SCHY group. Conclusion: Both HYYKF and ESCs improve the ovarian function of POI induced by VCD, and a combination of HYYKF and ESCs has the advantage that they work together to promote follicles developing probably by inhibiting expression of the TGF-β1/TAK1 pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Hyykf Extractmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synergistic effect of Huyang Yangkun Formula and embryonic stem cells on 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in mice

Xie

et al. 2020

Chin Med

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“…After the last VCD intraperitoneal injection, the rats in the VCD + DBT group received a 7.5 g/kg/day dose of DBT for 75 consecutive days. The dosage and duration of VCD and DBT were determined according to a previous article [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Danggui Buxue Tang Rescues Folliculogenesis and Ovarian Cell Apoptosis in Rats with Premature Ovarian Insufficiency

Wang

Liu

Nie

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Premature ovarian insufficiency (POI) is a common female endocrine disease that is closely linked to ovarian function. Danggui Buxue Tang (DBT) is a classic prescription of traditional Chinese medicine that is helpful for rescuing ovarian function. However, the mechanism by which DBT rescues ovarian function remains unclear. This study explored the molecular mechanism of DBT with respect to apoptosis and related signals in ovarian cells. The quality control of DBT was performed by HPLC. After DBT intervention in the POI rat model, serum AMH/FSH/LH/E2 levels were detected by ELISA, follicles at various developmental stages were observed by HE staining, apoptosis was detected by TUNEL, and the expression profiles of Bcl-2 family proteins and key proteins in the Jak2/Foxo3a signaling pathway were evaluated by western blot. The results demonstrated that DBT could encourage the development of primary/secondary/antral follicles and increase the secretion of AMH. Moreover, DBT might inhibit Foxo3a by upregulating Jak2, thereby mediating Bcl-2 family activities and inhibiting apoptosis in ovarian cells. In conclusion, DBT promotes follicular development and rescues ovarian function by regulating Bcl-2 family proteins to inhibit cell apoptosis, which could be related to the Jak2/Foxo3a signaling pathway.

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“…It was found that compared with DHEA, HYYKF obviously alleviated menopausal symptoms in patients especially in psychological and urogenital aspects, and significantly improved the level of E2. In an animal experiment, HYYKF significantly increased the number of antral follicles and mature follicles in 4-vinylcyclohexene diepoxide (VCD) induced POI rats, suggesting the advantages of HYYKF in promoting follicular development and maturity (Xie et al, 2019).…”

Section: Introductionmentioning

confidence: 97%

The Effect of Huyang Yangkun Formula on N6-methyladenosine Modification in 4-vinylcyclohexene diepoxide Induced Premature Ovarian Insufficiency Rats

Li¹,

Li²,

Liu³

et al. 2020

Preprint

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The aging of female reproductive system is mainly manifested by the decline of ovarian function, which is a physiological phenomenon. When it happens prematurely, it is called premature ovarian insufficiency(POI). Huyang Yangkun Formula(HYYKF) was developed according to theory of Chinese medicine and clinical experience and found to obviously relieve symptoms associated with menopause in POI patients. However, little is known about the effect of HYYKF on N6-methyladenosine (m 6 A) modification in ovaries of POI. In this study, VCD induced-POI model was established to investigate the effect of HYYKF on m 6 A modification. We found in the VCD-induced models, protein expressions of the m 6 A enzymes declined except that of FTO, and the expressions of METTL3, METTL14 and YTHDF1 declined very significantly. Interestingly, in naturally aging ovaries, the level of m 6 A declined very significantly at 9-week-old and 24-week-old, and the protein expression of METTL3, METTL14 and FTO in ovaries was down-regulated as mice aged. The date release that the level of m 6 A declines as the ovarian insufficiency occurs, which happens in both naturally aging ovaries and VCD-induced models. We found that HYYKF treatment promoted ovarian follicles development and the level of AMH in VCD induced-POI rats. Most importantly, HYYKF induced expressions of the m 6 A enzymes except that of FTO, and elevated the expressions of METTL3, METTL14, ALKBH5 and YTHDF1 significantly.

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Huyang yangkun formula protects against 4-Vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats via the Hippo–JAK2/STAT3 signaling pathway

Cited by 17 publications

References 42 publications

Synergistic effect of Huyang Yangkun Formula and embryonic stem cells on 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in mice

Synergistic effect of Huyang Yangkun Formula and embryonic stem cells on 4-vinylcyclohexene diepoxide induced premature ovarian insufficiency in mice

Danggui Buxue Tang Rescues Folliculogenesis and Ovarian Cell Apoptosis in Rats with Premature Ovarian Insufficiency

The Effect of Huyang Yangkun Formula on N6-methyladenosine Modification in 4-vinylcyclohexene diepoxide Induced Premature Ovarian Insufficiency Rats

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